A cell membrane is an essential factor for maintaining a cell, and membrane proteins localized in the cell membrane play an important role in intracellular and extracellular communication through dynamic interaction with ligands. Substantially, about a half of cellular proteins are known to be able to interact with ligands in the cell membrane, but huge parts still remain unknown. To figure out such interactions, a variety of techniques and attempts have been conducted over the years, and researchers are still making efforts.
Since an extracellular environment has a relatively very small viscosity, compared to an inside of the cell membrane, the influence of an extracellular domain of the membrane protein which directly binds to ligands on the diffusivity of target proteins has been ignored, and many researches relating to the diffusion theory of membrane proteins, which is the Saffman-Delbruck model, focus on a transmembrane domain to determine such diffusivity of the membrane proteins and describe its importance on membrane protein diffusion. Therefore, it has been considered that it is fundamentally difficult to measure the binding of ligands to the extracellular domain of the target membrane protein based on diffusion of membrane protein. However, since a system used in the conventional research could measure the interaction between target membrane protein and ligand only in an artificial and controlled environment using purified membrane proteins in vitro or inserting the target membrane protein into an artificially formed lipid membrane, such previous researches cannot reflect the complicated structure of an actual cell membrane, and thus the analysis of the interactions involving extracellular domain of membrane proteins with ligands has been limited.